# Stability and flexibility of neural representations in the ventral striatum

> **NIH NIH R01** · HARVARD UNIVERSITY · 2024 · $682,814

## Abstract

The olfactory tubercle (OT) is a ventral striatal brain region implicated in reward processing and motivated
behaviors including addiction. It receives olfactory sensory input, as well as strong dopaminergic innervation
from the ventral tegmental area (VTA). Learning-induced changes in neural activity can occur rapidly and
differentially in distinct types of neurons on the OT, but it is not clear how stable these changes in
representations are. Recent studies in many brain regions have revealed a surprising instability in sensory
representations, even when the animal’s behavior is stable. Unstable representations are hypothesized to
potentially arise from ongoing synaptic plasticity, as might occur with ongoing activity or further learning.
Whether such “representational drift” is present in striatal areas including the OT is unknown and will be a
subject of inquiry in this proposal. The PIs will ask whether OT neural representation of previously learned
associations is stable when new associations are learned, and whether the representations are altered
when old associations are unlearned or degraded. The PIs will use deep brain multiphoton imaging at
subcellular resolution to monitor activity in identified subtypes of OT neurons over weeks as mice learn and
maintain odor-outcome associations. Using our collective expertise in behavior, physiology, and imaging,
the PIs will tackle the following Aims. Aim 1: To determine whether neural representations of cue-outcome
associations in the OT are stable over several days. The PIs will train mice to learn the arbitrarily assigned
valence of several odors and track the activity of two cardinal types of neurons in the OT in behaving mice
during and after task learning over multiple weeks. The PIs hypothesize that continuous experience and
reinforcement will stabilize representations in the OT, which can degrade with pauses in experience. Aim 2:
To determine whether and how existing representations in the OT change when new cue-outcome
associations are learned. After mice have stably associated several odors with specific outcomes, the PIs
will introduce new odors to be learned, reverse or extinguish familiar associations, as specific OT neural
populations are tracked. The PIs hypothesize that new learning will lead to greater representational drift for
older, familiar associations. Aim 3: To determine the role of dopaminergic signaling in maintaining stability
and flexibility of representations in the OT. Whether continued dopamine signaling in the OT helps maintain
stable representations through repetition or perturbs stability by promoting additional synaptic plasticity is
unknown. The PIs will perturb dopaminergic signaling to the OT in mice that have learned cue-outcome
associations and investigate how neural representations in the OT evolve. The PIs hypothesize that
perturbing dopamine signaling will degrade representational stability even with continued experience. Our
studies, in addition to answ...

## Key facts

- **NIH application ID:** 10902726
- **Project number:** 2R01DC017311-06
- **Recipient organization:** HARVARD UNIVERSITY
- **Principal Investigator:** VENKATESH N MURTHY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $682,814
- **Award type:** 2
- **Project period:** 2019-03-01 → 2029-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10902726

## Citation

> US National Institutes of Health, RePORTER application 10902726, Stability and flexibility of neural representations in the ventral striatum (2R01DC017311-06). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10902726. Licensed CC0.

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